Research Abstracts from the December Meeting of the American Society of Hematology

Jeff Cornett RN MSN, Director of Research, Training & Advocacy

The American Society of Hematology (ASH) held its Annual Meeting and Exposition in San Francisco on December 6–9, 2014. Each speaker who presented a research report at the meeting also wrote an abstract:  a short description of the research question, the methods used to investigate it, and the results. ASH posts these abstracts online for interested persons to read. You can browse all of the abstracts by keyword, such as hemophilia or von Willebrand Disease. This article will highlight three abstracts addressing important topics in hemophilia.

The Impact of Being Overweight on Factor VIII Dosing in Children
The patient’s body weight is used to calculate the dose of factor concentrate. Using the traditional method, the more a patient weighs, the higher the dosage of factor concentrate given. Researchers are challenging this equation -- based on the knowledge that very little factor VIII leaves the veins and arteries in the body. In other words, why dose based on body fat when the circulatory system is what matters?

This type of study is not easy to accomplish because it involves giving a dose of factor and then drawing blood at set time points to see how high the level of factor VIII has risen in the blood. It is difficult to get anyone, especially children, to agree to be stuck with a needle so many times. Researchers in Brussels, Belgium, overcame this hurdle by using data that had already been collected from children participating in clinical trials to test factor products. They divided the children into two groups: one group that was normal or underweight and another group that was overweight or obese. The group that was overweight had significantly higher levels of factor VIII in their blood after taking a dose of factor concentrate, even though all dosages were calculated using the same formula. Using body weight to calculate the dose resulted in overweight children receiving more factor concentrate than was needed to achieve the desired level of factor in the blood.

The researchers called for a change in the way factor dosages are calculated for overweight children; for example, dosing based on ideal or adjusted body weight instead of actual body weight. These alternative ways of calculating the factor dose will need to be assessed to determine the most accurate method. This is not a safety issue. There is little evidence that a temporary higher level of factor in the blood poses any health risk. It is an economic issue. Factor concentrate is priced in units. Right now, the more you weigh, the more units of factor you are given. Reducing the number of units given can save thousands of dollars in factor costs each year.

The Changing Costs of Caring for Hemophilia Patients in the U.S.
The cost of hemophilia care was the topic of an abstract by researchers at Biogen Idec, a company that makes factor concentrate. They were interested in seeing how the cost of treating hemophilia changed over a person’s lifespan as well as how hemophilia treatment and costs have changed in the past decade.

The researchers used data from U.S. insurance claims between January 2004 and December 2012. They looked at insurance data from men who had two or more claims for a hemophilia drug within a three-month period and who were enrolled in an insurance plan for at least 180 days. Patients who were being treated for inhibitors were not included. Insurance data from a total of 626 men with hemophilia A and 136 men with hemophilia B were analyzed.

As expected, the cost of hemophilia care rose during the first three decades of a patient’s life (as a patient grows, his body weight increases and he requires higher doses of factor). The yearly cost peaked for hemophilia A patients at age 36 ($363,948) and at age 29 for hemophilia B patients ($453,179). The annual cost then went down in a patient’s thirties and forties.

The number of days for which factor concentrate was supplied to a patient rose significantly between 2007 and 2012. For example, in 2007 enough Advate® (factor VIII concentrate) was dispensed for a patient to treat 156.5 days. By 2012, this number had risen to 251 days. A significant trend was also seen for hemophilia B:  Benefix® was dispensed for 86 days of treatment in 2007 and for 215 days in 2012. The researchers believe these changes may indicate that more patients are treating prophylactically (taking factor regularly to prevent bleeding instead of waiting until a bleed occurs). Prophylactic treatment is considered the optimal therapy for people with severe hemophilia according to the Medical and Scientific Advisory Council of the National Hemophilia Foundation.

Factor VIII Gene Variants and Inhibitor Risk in African American Hemophilia A Patients
Sometimes when a person with hemophilia takes factor concentrate, his body’s immune system will react against the factor protein by forming antibodies that attack the factor. These “neutralizing antibodies” are called inhibitors. They occur in 20 to 30% of patients with severe hemophilia A.  Inhibitors occur more frequently in African Americans and researchers are working to discover why.

One concern has been that the human factor VIII genes used to manufacture recombinant factor concentrate are “mismatched” to the factor VIII normally produced by African Americans. A group of hemophilia researchers from across the country, part of the Personalized Approaches to Therapies for Hemophilia (PATH) study, looked closely at this possibility. Through detailed analysis, they concluded that the immune system response to three potential points of “mismatched” factor VIII is “unlikely to contribute appreciably to the overall inhibitor incidence in African Americans” with severe hemophilia A. They called for more research on the topic, particularly focusing on understanding causes for the higher risk of inhibitors among African Americans with a factor VIII gene intron-22 inversion compared with Caucasians who have the same factor VIII gene defect.